Identification of novel oligodendroglioma‐associated candidate tumor suppressor genes in 1p36 and 19q13 using microarray‐based expression profiling

• Published in: International journal of cancer Vol. 119; no. 4; pp. 792 - 800
• Main Authors: Tews, Bjoern, Felsberg, Joerg, Hartmann, Christian, Kunitz, Annegret, Hahn, Meinhard, Toedt, Grischa, Neben, Kai, Hummerich, Lars, von Deimling, Andreas, Reifenberger, Guido, Lichter, Peter
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.08.2006; Wiley-Liss
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Child; Chromosomes, Human, Pair 1 - genetics; Chromosomes, Human, Pair 19 - genetics; DNA microarray; DNA, Complementary - genetics; Down-Regulation; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; loss of heterozygosity; Male; Medical sciences; Middle Aged; Neurology; oligodendroglioma; Oligodendroglioma - genetics; Oligonucleotide Array Sequence Analysis; Transcription, Genetic - genetics; tumor suppressor gene; Tumor Suppressor Proteins - genetics; Tumors; Tumors of the nervous system. Phacomatoses; Up-Regulation; Chromosomal aberration; Human; Nervous system diseases; Allelic imbalance; DNA chip; Malignant tumor; Carcinogenesis; Oligodendroglioma; Gene expression profile; DNA microarray; Malignant glioma; Abnormal chromosome F19; Cancerology; Central nervous system disease; Abnormal chromosome A1; Loss of heterozygosity; Cytogenetics; Abnormal chromosome; Genetics; Candidate gene; gene expression profiling; Tumor suppressor gene
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.21901

Loss of heterozygosity (LOH) on chromosomal arms 1p and 19q is the most common genetic alteration in oligodendroglial tumors and associated with response to radio‐ and chemotherapy as well as favorable prognosis. Using microsatellite analysis, we previously identified the chromosomal regions 1p36.22‐p36.31 and 19q13.3, as candidate tumor suppressor gene regions being commonly deleted in these tumors. To identify genes within these regions that are downregulated in oligodendroglial tumors with LOH 1p/19q, we performed cDNA microarray‐based RNA expression profiling of 35 gliomas with known allelic status on 1p and 19q, including 7 oligodendrogliomas and 8 diffuse astrocytomas of World Health Organization (WHO) grade II, as well as 14 anaplastic oligodendrogliomas and 6 anaplastic oligoastrocytomas of WHO grade III. The microarrays used for expression profiling carried ∼7,000 gene‐specific cDNAs, with complete coverage of the genes located in 1p36.13‐p36.31 and 19q13.2‐q13.33. Microarray analysis identified 8 genes from these regions (MGC4399, SRM, ICMT, RPL18, FTL, ZIN, FLJ10781 and DBP), which all showed significantly lower expression in 1p/19q‐deleted gliomas when compared to gliomas without 1p/19q losses. Quantitative real‐time reverse transcription‐PCR analyses were performed for the MGC4399, ICMT and RPL18 genes and confirmed the microarray findings. In addition, we found that the cytosolic phospholipase A2 (PLA2G4C) gene at 19q13.3 demonstrated significantly lower expression in anaplastic oligodendrogliomas (WHO grade III) when compared to well‐differentiated oligodendrogliomas (WHO grade II). Taken together, our study provides a set of interesting novel candidate genes that may play important roles in the pathogenesis of oligodendroglial tumors. © 2006 Wiley‐Liss, Inc.